The Mutations and Clinical Variability in Maternally Inherited Diabetes and Deafness: An Analysis of 161 Patients

Front Endocrinol (Lausanne). 2021 Nov 25:12:728043. doi: 10.3389/fendo.2021.728043. eCollection 2021.


Aims: To investigate the clinical features and mitochondrial mutations for maternally inherited diabetes and deafness.

Methods: PubMed, Embase, Medline, Web of Science, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: "Maternally inherited diabetes and deafness" OR "MIDD" OR "Mitochondrial diabetes". The mutations and clinical features were analyzed. Correlation between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes was conducted by Spearman test. The significance level was set as p < 0.05. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows.

Results: Totally 161 patients with 21 different mitochondrial mutations were enrolled. The most common mutation was the m.3243A>G mutation in 136 cases. Of 142 patients, 120 (84.51%) had family histories of diabetes or hearing loss. Hearing loss presented in 85.71% of the patients with mitochondrial mutations. Central nervous system diseases were found in 29.19%, myopathy in 22.98%, oculopathy in 23.60%, cardiac disease in 23.60%, and nephropathy in 13.66% of the patients. Forty-two of 101 (41.58%) patients were underweight. A significant negative correlation was found between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes.

Conclusions: The young onset of diabetes with low or normal BMI, maternal inheritance, and presence of impairments of multiple systems should prompt a genetic testing in order to differentiate MIDD from other types of diabetes earlier.

Keywords: diagnosis; heteroplasmy; maternally inherited diabetes and deafness; mitochondrial gene mutations; treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biological Variation, Population
  • Cohort Studies
  • DNA, Mitochondrial / genetics*
  • Deafness / epidemiology
  • Deafness / genetics*
  • Deafness / pathology*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology*
  • Genetic Heterogeneity
  • Humans
  • Infant, Newborn
  • Mitochondrial Diseases / epidemiology
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology*
  • Mutation
  • Phenotype


  • DNA, Mitochondrial

Supplementary concepts

  • Noninsulin-dependent diabetes mellitus with deafness